This project involves an electron spin resonance study of the mechanism through which spin labeled derivatives of morphine bind to the opiate receptor site. A series of new spin labeled drugs are being synthesized for these investigations. The labeled drugs will be bound to synaptic membranes and esr spectroscopy used to determine changes in motional correlation times as a function of the drugs structure. The results will be analyzed to determine the geometry by which these drugs bind to the opiate receptor site. Structure-activity relationships will be correlated with binding geometry to determine how analgesic activity varies as a function of binding geometry. Studies will also be conducted with a series of model membranes to obtain information on the mechanism of binding to probable constituents of the opiate receptor site. Spin labeled lipids will be introduced into synaptic membranes and esr spectroscopy used to determine changes in membrane structure when an opiate in bound. The overall goal of this research is a determination of the geometry of the opiate receptor site and the mechanism by which these drugs act on the central nervous system.